{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T05:57:33Z","timestamp":1789883853950,"version":"4.0.1"},"reference-count":36,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2018,11,1]],"date-time":"2018-11-01T00:00:00Z","timestamp":1541030400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"},{"start":{"date-parts":[[2018,11,1]],"date-time":"2018-11-01T00:00:00Z","timestamp":1541030400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2018,12]]},"abstract":"<jats:p>Erythrocytes bind circulating immune complexes (ICs) and facilitate IC clearance from the circulation. Chronic hepatitis C virus (HCV) infection is associated with IC\u2010related disorders. In this study, we investigated the kinetics and mechanism of HCV and HCV\u2010IC binding to and dissociation from erythrocytes. Cell culture\u2010produced HCV was mixed with erythrocytes from healthy blood donors, and erythrocyte\u2010associated virus particles were quantified. Purified complement proteins, complement\u2010depleted serum, and complement receptor antibodies were used to investigate complement\u2010mediated HCV\u2010erythrocyte binding. Purified HCV\u2010specific immunoglobulin G (IgG) from a chronic HCV\u2010infected patient was used to study complement\u2010mediated HCV\u2010IC\/erythrocyte binding. Binding of HCV to erythrocytes increased 200\u2010 to 1,000\u2010fold after adding complement active human serum in the absence of antibody. Opsonization of free HCV occurred within 10 minutes, and peak binding to erythrocytes was observed at 20\u201030 minutes. Complement protein C1 was required for binding, whereas C2, C3, and C4 significantly enhanced binding. Complement receptor 1 (CR1, CD35) antibodies blocked the binding of HCV to erythrocytes isolated from chronically infected HCV patients and healthy blood donors. HCV\u2010ICs significantly enhanced complement\u2010mediated binding to erythrocytes compared to unbound HCV. Dissociation of complement\u2010opsonized HCV from erythrocytes depended on the presence of Factor I. HCV released by Factor I bound preferentially to CD19<jats:sup>+<\/jats:sup> B cells compared to other leukocytes. <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic> These results demonstrate that complement mediates the binding of free and IC\u2010associated HCV to CR1 on erythrocytes and provide a mechanistic rationale for investigating the differential phenotypic expression of HCV\u2010IC\u2013related disease.<\/jats:p>","DOI":"10.1002\/hep.30087","type":"journal-article","created":{"date-parts":[[2018,5,9]],"date-time":"2018-05-09T23:45:11Z","timestamp":1525909511000},"page":"2118-2129","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":14,"title":["Binding of Free and Immune Complex\u2010Associated Hepatitis C Virus to Erythrocytes Is Mediated by the Complement System"],"prefix":"10.1097","volume":"68","author":[{"given":"Kazi Abdus","family":"Salam","sequence":"first","affiliation":[{"name":"Infectious Diseases Section, Department of Transfusion Medicine, Clinical Center,National Institutes of Health,Bethesda,MD"},{"name":"Department of Biochemistry and Molecular Biology,University of Rajshahi,Rajshahi,Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard Y.","family":"Wang","sequence":"additional","affiliation":[{"name":"Infectious Diseases Section, Department of Transfusion Medicine, Clinical Center,National Institutes of Health,Bethesda,MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Grandinetti","sequence":"additional","affiliation":[{"name":"Infectious Diseases Section, Department of Transfusion Medicine, Clinical Center,National Institutes of Health,Bethesda,MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"De Giorgi","sequence":"additional","affiliation":[{"name":"Infectious Diseases Section, Department of Transfusion Medicine, Clinical Center,National Institutes of Health,Bethesda,MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harvey J.","family":"Alter","sequence":"additional","affiliation":[{"name":"Infectious Diseases Section, Department of Transfusion Medicine, Clinical Center,National Institutes of Health,Bethesda,MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert D.","family":"Allison","sequence":"additional","affiliation":[{"name":"Infectious Diseases Section, Department of Transfusion Medicine, Clinical Center,National Institutes of Health,Bethesda,MD"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2018,11,1]]},"reference":[{"key":"hep30087-bib-0001-20241017","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1002\/hep.26141","article-title":"Global epidemiology of hepatitis C virus infection: new estimates of age\u2010specific antibody to HCV 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